TACHYKININ NK-2 RECEPTORS IN CHILD URINARY-BLADDER

Purpose: Although NK-2 receptors mediate contractions to tachykinins i n adult detrusor muscle, little is known about the functions of tachyk inins in child urinary bladder. Here we have used highly selective ago nists and antagonists to examine NK-2 receptors in child detrusor musc le. Materials and Methods: Specimens of urinary bladder from 23 childr en (0 to 10 years) were obtained at operation for vesicoureteric reflu x. Strips of detrusor muscle were mounted in organ baths in Krebs solu tion containing phosphoramidon (10 mu M.), and isometric tension was r ecorded. Contractile responses were elicited by tachykinins and select ive agonists in the presence and absence of autonomic inhibitors and o f tachykinin NK-2 receptor antagonists. Results: The NK-2 receptor ago nists neurokinin A (NKA), neuropeptide gamma and [Lys(5),MeLeu(9),Nle( 10)]-NKA(4-10) contracted the isolated child detrusor, with pD(2) valu es of 7.7, 7.2 and 7.3. The maximum response to NKA was greater than t hat to the other 2 agonists. No age-related differences were seen. Sel ective agonists for NK-1 receptors ([Sar(9),Met(O-2)(11)]-SP and septi de) and NK-3 receptors (senktide) were ineffective contractile agents, Responses to NKA. were unaffected by phentolamine (5 mu M.), atropine (5 mu M.), propranolol (3 mu M.), tetrodotoxin (1 mu M.) and indometh acin (1 mu M.), indicating a direct action on smooth muscle. The tachy kinin NK-2 receptor antagonists SR 48968 and MEN 10627 caused a concen tration-dependent antagonism of responses to NKA, with apparent pK(B) values of 9.4 and 8.1. Conclusions: Neurokinin A appears to act direct ly on NK-2 receptors on detrusor muscle of infant and child urinary bl adder, without involvement of neural or indirect contractile mechanism s. Potency of antagonists was similar to that seen in other tissues. H owever, agonist potency was significantly lower in the isolated detrus or from children, compared with our previous study in adult detrusor. This discrepancy may be related to age-related differences in NK-2 rec eptors or in contractile mechanisms; alternatively it may be a result of the reflux condition.